Phenotypic Correlations with Circulating Tyrosine and a Novel TAT Mutation：a Case Report and Literature Review of Tyrosinemia Type II

<title>Abstract</title> <p>Background Tyrosinemia type II (Richner-Hanhart syndrome) results from a deficient activity of tyrosine aminotransferase (TAT), defining an ultrarare autosomal recessive metabolic disorder. While fewer than 200 cases have been reported worldwide, the number of cases described in China is markedly lower. The causative TAT gene resides on chromosome 16q22, encompasses 12 exons, and yields the 454–amino acid TAT enzyme. Methods We present a case of tyrosinemia type II harboring a previously unreported homozygous TAT mutation, specifically a homozygous missense mutation (c.689T &gt; C), in a 5-year-old patient manifesting classic palmoplantar hyperkeratosis and ocular lesions. Analysis of 12 comparable cases from the literature corroborated a distinct clinical profile: invariable ocular lesions, frequent diagnostic delay or error, a 50% rate of parental consanguinity, and consistently elevated tyrosine levels (often &gt; 1000 µmol/L). To strengthen the analysis, we integrated our data with the 2017 cohort from Peña-Quintana and colleagues. Results This combined dataset demonstrated strong correlations between tyrosine levels and multisystem involvement, yielding Spearman coefficients of 0.949 for ocular, 0.800 for cutaneous, and 0.600 for neurological manifestations. Conclusions This study contributes to both clinical practice and pathophysiological understanding. It aids clinicians in recognizing the full phenotypic spectrum of tyrosinemia type II to reduce diagnostic errors, and provides supporting evidence for the association between circulating tyrosine concentrations and clinical disease expression, highlighting avenues for future research.</p>